A research team at Tulane University, New Orleans, Louisiana has reported that the application
of high levels of oxygen to a severed bone facilitates bone regrowth, study results that may one day hold promise for individuals with amputations such as injured soldiers, patients with diabetes, and other accident victims.
The only vertebrate capable of regenerating lost limbs are salamanders and newts. However, the work spearheaded by Mimi Sammarco, PhD, a research assistant professor at Tulane, uses a mouse model. “While salamanders are able to regenerate entire limbs, rodents, monkeys, and humans are only able to regenerate the digit tip after amputation,” she said. Multiple research teams have been trying to determine what makes that difference between regrowth anywhere toward the tip of the finger, but no regrowth further down. The Tulane lab has been investigating which genes are turned on, which proteins are expressed, and which molecular activities change at the site of amputation over time.
“What it boils down to is genes (that spur regeneration) don’t just turn themselves on,” Sammarco said. “They turn on because something signals them. So I thought, maybe it’s oxygen that’s turning them on. Oxygen is often the primary signal that turns on various genes.”
Sammarco used a special incubator to expose a thin bone sample taken from an amputation site to high levels of oxygen. “What we found is that when you expose regenerating bone to 20 percent oxygen, it’ll respond very favorably but only at a certain time. If you try it too early, like right after amputation, it doesn’t do a whole lot.”
The air we breathe is made of about 20 percent oxygen, while the level in the body is closer to around 6 percent, she said. “In some areas of injury, the oxygen level is going to go down to 1 percent,” because the blood vessels that deliver oxygen to tissue naturally retract after injury.
Many researchers are trying to figure out how to reinvigorate vasculature and how to oxygenate the wound site. There are two opposing fields, Sammarco said. “We get injured, so we need to drop the oxygen concentration to encourage vasculature. And then there’s the other side that says, no, we need to flood it with oxygen to oxygenate the tissue. And neither works particularly well. I think you have to know when to apply each one…. There’s a sequence in growing things back. And oxygen can push the button that has to be applied at a certain time.”
Sammarco said that the goal is to eventually make this treatment available to wounded warriors and the general public alike, in a manner that is portable and usable. “Every effort to direct and control the extension of amputation stump length contributes to the rehabilitation of amputees, while keeping in mind the long-term goal of complete regeneration,” she said.
